Abstract
BackgroundImmune-related enterocolitis (irEC) is the most common serious complication from checkpoint inhibitors (CPIs). The current front-line treatment for irEC, high-dose corticosteroids (CS), have significant side effects and prolonged therapy may reduce CPI-anti-tumor activity. Early addition of TNF-α inhibitors such as infliximab (IFX) may expedite symptom resolution and shorten CS duration. Thus, we conducted the first retrospective study, to our knowledge, evaluating symptom resolution in patients with irEC treated with and without IFX.MethodsData were collected from the medical records of patients diagnosed with irEC. The primary endpoint was time to symptom resolution for irEC for cases managed with IFX plus CS (IFX group) versus CS alone (CS group). Duration of CS, overall survival (OS), and time to treatment failure (TTF) were secondary endpoints.ResultsAmong 75 patients with irEC, 52% received CS alone, and 48% received IFX. Despite higher grade colitis in the IFX group (grade 3/4: 86% vs. 34%; p < 0.001), median times to diarrhea resolution (3 vs. 9 days; p < 0.001) and to steroid titration (4 vs. 13 days; p < 0.001) were shorter in the IFX group than in the CS group without a negative impact on TTF or OS. Total steroid duration (median 35 vs. 51 days; p = 0.150) was numerically lower in the IFX group.ConclusionsDespite higher incidence of grade 3/4 colitis, IFX added to CS for the treatment of patients with irEC was associated with a significantly shorter time to symptom resolution. The data suggest that early introduction of IFX should be considered for patients with irEC until definitive prospective clinical trials are conducted.
Highlights
Immune-related enterocolitis is the most common serious complication from checkpoint inhibitors (CPIs)
Patient characteristics A total of 75 patients with Immune-related enterocolitis (irEC) were included in the study (Fig. 1)
The median age at the development of irEC was 63 years in patients treated with CS alone and 61 years in patients treated with IFX plus CS
Summary
Study design Adult cancer patients treated with CPIs (ipilimumab, tremelimumab, nivolumab, pembrolizumab, atezolizumab, or ipilimumab-nivolumab in combination) between January 1, 2012, and June 30, 2017, were identified by review of the institutional pharmacy database at MD Anderson Cancer Center. Patients who received IFX and CS (dexamethasone, methylprednisolone, and prednisone) as well as those who received CS alone were identified Their records were reviewed to identify the indication for those treatments, and patients who received IFX and/or CS for a reason other than irEC were excluded from further analysis. Stool studies for infectious cause, endoscopic and radiographic evaluations, immunosuppressant regimens, CS duration, number of IFX doses, and treatment side effects were documented. IrEC was defined as diarrhea requiring immunosuppressants in the setting of CPI therapy and was graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 based. Statistical analysis Patient characteristics were reported as percentages for categorical variables and as medians for continuous variables.
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